Development and Validation of a Noninvasive Model for the Detection of High-Risk Varices in Patients with Unresectable HCC.

BACKGROUND AND AIMS: Non-invasive variceal risk stratification systems have not been validated in patients with hepatocellular carcinoma (HCC), which presents logistical barriers for patients in the setting of systemic HCC therapy. We aimed to develop and validate a non-invasive algorithm for the prediction of varices in patients with unresectable HCC. METHODS: We performed a retrospective cohort study in 21 centers in the US including adult patients with unresectable HCC and Child Pugh A5-B7 cirrhosis diagnosed between 2007 and2019. We included patients who completed an esophagogastroduodonoscopy (EGD) within 12 months of index imaging but prior to HCC treatment. We divided the cohort into a 70:30 training set and validation set, with the goal of maximizing negative predictive value (NPV) to avoid EGD in low-risk patients. RESULTS: We included 707 patients (median age 64.6 years, 80.6% male and 74.0% White). Median time from HCC diagnosis to EGD was 47 (IQR: 114) days, with 25.0% of patients having high-risk varices. A model using clinical variables alone achieved a NPV of 86.3% in the validation cohort, while a model integrating clinical and imaging variables had an NPV 97.4% in validation. The clinical and imaging model would avoid EGDs in over half of low-risk patients while misclassifying 7.7% of high-risk patients. CONCLUSION: A model incorporating clinical and imaging data can accurately predict the absence of high-risk varices in patients with HCC and avoid EGD in many low-risk patients prior to the initiation of systemic therapy, thus expediting their care and avoiding treatment delays.

Copeptin plus troponin in the rapid rule out of acute myocardial infarction and prognostic value on post-myocardial infarction outcomes: a systematic review and diagnostic accuracy study.

BACKGROUND: A critical and unmet therapeutic need is the prompt and reliable exclusion of acute myocardial infarction (AMI), which would allow for prompt discharge from the emergency department. High-sensitivity troponin (HS-TnT) combined with copeptin has been proposed to expedite the diagnostic exclusion of AMI in addition to its predictive usefulness in the intermediate and long-term outcomes of AMI. The European Society of Cardiology recommends the Global Registry of Acute Coronary Events (GRACE) as a prognostic score to manage acute coronary syndrome (ACS) without ST segment elevation. The purpose of this study was to compare the diagnostic accuracy of HS-TnT combined with copeptin in ruling out AMI compared to HS-TnT alone. By combining a low GRACE score (108) with negative HS-TnT (14 ng/L) and copeptin (14 pmol/L), non-ST and ACS were reliably ruled out, including non-ST segment elevation MI and unstable angina. RESULTS: The present research included nine studies with a total of 13,232 participants. The negative predictive value (NPV) for copeptin and HS-TnT was found to be slightly higher in combination (62-99%) than for HS-TnT alone (60-99%). The sensitivity of copeptin ranged from 0% to 100%, with a pooled sensitivity of 0.79 (CI 95% 0.76, 0.82). The specificity of copeptin ranged from 13% to 100%, with a pooled specificity of 0.89 (CI 95% 0.85, 0.91), a pooled positive likelihood ratio (PLR) of 9.86 (CI 95% 4.42, 22.02), and a pooled negative likelihood ratio (NLR) of 0.08. (95% CI 0.01, 0.44). CONCLUSIONS: The use of combined negative copeptin and highly sensitive troponin testing in low-to-intermediate risk patients with suspected acute coronary syndrome resulted in a quick discharge with a safe and rapid rule out of non-ST + ACS.

Transient diabetes insipidus after vasopressin discontinuation in cystic fibrosis with septic shock.

Central diabetes insipidus (DI) is an uncommon condition caused by reduced or lack of vasopressin secretion from the posterior pituitary gland, typically caused by gland destruction. Several other causes for central DI have also been proposed. Here we present a case of transient central DI after discontinuation of vasopressin used for septic shock without evidence of overt pituitary damage in a cystic fibrosis patient. The serum sodium concentration peaked at 137 mmol/L in the setting of polyuria within 3 days of vasopressin discontinuation without other identified alternative etiologies. Sodium levels and urine output trended down dramatically with desmopressin administration.

The Use of Midodrine as an Adjunctive Therapy to Liberate Patients from Intravenous Vasopressors: A Systematic Review and Meta-analysis of Randomized Controlled Studies.

BACKGROUND: Studies evaluating the role of midodrine as an adjunctive therapy to liberate patients with shock from intravenous (IV) vasopressors have yielded mixed results. The aim of our study was to evaluate the efficacy and safety of midodrine as an adjunctive therapy to liberate patients with shock from IV vasopressors. METHODS: Electronic searches of the MEDLINE, EMBASE, and Cochrane databases through April 2022 for randomized controlled trials (RCTs) that evaluated the use of midodrine versus control in patients with shock and a low dose of IV vasopressors. The primary outcome was total IV vasopressor time, while the secondary outcomes included time-to-IV vasopressor discontinuation, IV vasopressor restart, intensive care unit (ICU) length of stay (LOS), hospital LOS, and incidence of bradycardia. RESULTS: The final analysis included four RCTs with a total of 314 patients: 158 in the midodrine group and 156 in the control group, with a weighted mean age of 64 years (54.2% men). There was no significant difference in the total IV vasopressor time between the midodrine and control groups (standardized mean difference [SMD] - 0.53; 95% confidence interval [CI] - 1.38 to 0.32, p = 0.22; I2 = 92%). Also, there were no significant differences between the two groups in the time-to-IV vasopressor discontinuation (SMD - 0.05; 95% CI - 0.57 to 0.47, p = 0.09), IV vasopressor restart (19.3 vs. 28.3%; risk ratio [RR] 0.74; 95% 0.25-2.20, p = 0.59), ICU LOS (SMD - 0.49; 95% CI - 1.30 to 0.33, p = 0.24), and hospital LOS (SMD 0.01; 95% CI - 0.27 to 0.29, p = 0.92). However, compared with the control group, the midodrine group had a higher risk of bradycardia (15.3 vs. 2.1% RR 5.56; 95% CI 1.54-20.05, p = 0.01). CONCLUSIONS: Among patients with vasopressor-dependent shock, midodrine was not associated with early liberation of vasopressor support or shorter ICU or hospital length of stay. Adding midodrine increased the risk of bradycardia. Further large RCTs are needed to better evaluate the efficacy and safety of midodrine in liberating patients from IV vasopressors.

Pleural Effusions in Patients With Congestive Heart Failure: Frequency, Pathogenesis, Diagnosis, and Implications.

Patients with cardiac disease frequently develop pleural effusions; the incidence is approximately 500,000 cases per year in the United States. These effusions often represent important clinical events for patients, indicating that either there has been an acute change in the patient's clinical status or the patient's chronic management program needs review. These effusions usually develop in both the right and left hemithorax but can be unilateral. The pathogenesis involves increased fluid transfer from parietal pleural capillaries into the pleural space and possibly decreased pleural fluid uptake into parietal pleural lymphatic structures. The increased fluid transfer develops due to increased capillary pressure secondary to elevated venous outflow pressure and secondary to decreased lymphatic flow into central vessels secondary to heart failure. Most pleural effusions associated with heart failure are transudates, but 20% to 25% have increased protein and lactate dehydrogenase levels suggesting an exudative process. Additional testing can clarify the situation and requires calculation of the serum albumin to pleural fluid albumin gradient or measurement of N-terminal pro-brain natriuretic peptide in the pleural fluid. An albumin gradient of greater than 1.2 g/dL suggests that the fluid is a transudate. The presence of a pleural effusion in a hospitalized patient at discharge is associated with an increased likelihood of rehospitalization and mortality within the next year. Patients with large symptomatic pleural effusions may require therapeutic thoracentesis. Recurrence of symptomatic effusions presents a management dilemma that might require repeated thoracenteses, indwelling intrapleural catheter placement, or other management steps used in advanced chronic heart failure.

Ustekinumab dose escalation improves clinical responses in refractory Crohn's disease.

BACKGROUND: Clinicians often utilize off-label dose escalation of ustekinumab (UST) in Crohn's disease (CD) patients with disease refractory to standard dosing. Previous studies report mixed results with dose escalation of UST. METHODS: A retrospective observational study of 143 adult patients with CD receiving UST over a 33-month time period was conducted. Patients receiving UST at standard dosage for a minimum of 16 weeks were included in the analysis. Primary outcomes collected were clinical response [Physician Global Assessment Score (PGA) by >1] and remission (PGA = 0). Changes in clinical parameters were calculated for dose-escalated patients beginning with the time of dose switch (~42 weeks) and compared with a group of patients who were classified as "failing" standard dosing at 42 weeks who were not dose escalated. RESULTS: Dose escalation improved PGA by 0.47 ± 0.19 compared with patients remaining on every 8 weeks dosing (Q8 week), who worsened by 0.23 ± 0.23 (p < 0.05). Dose escalation decreased CRP 0.33 ± 0.19 mg/L and increased serum albumin 0.23 ± 0.06 g/dL (p < 0.05). Surprisingly, disease duration and prior CD surgeries inversely correlated with the need for dose escalation. CONCLUSION: Our results support UST Q4 week dose escalation for selected CD patients who fail to achieve remission on standard Q8 week dosing. Dose escalation improves clinical outcomes, prevents worsening disease severity, and positively impacts CRP and albumin levels. Together these data indicate that clinicians should attempt Q4 week UST dosing in refractory CD patients before switching to an alternative class of biologic therapy.

A Rare Case Report of Extra-adrenal Pheochromocytoma with Normal Blood Pressure: Is that Possible?

Extra-adrenal pheochromocytoma is uncommon and usually secreting nor-epinephrine. We are presenting a possible case of extra-adrenal pheochromocytoma in a 68-year-old male who was admitted to Queens Hospital Center complaining of shortness of breath for two days. Physical examination was unremarkable except tachycardia. Ventilation/perfusion (V/Q) scan showed the intermediate probability for pulmonary thromboembolism. Computed tomography (CT) chest confirmed the presence of old embolism and showed the 1.1 cm nodule in the left upper lobe. He suddenly collapsed and went into cardio-respiratory failure and attempts to resuscitate were futile. Results for pheochromocytoma workup received after the patient has passed away and it showed elevated levels of 24-hour urine metanephrine, normetanephrine, and Vanillylmandelic acid (VMA). In our patient, CT abdomen did not identify any mass in the adrenal gland or at the bifurcation of the aorta. The extra-adrenal tumor can secrete enough epinephrine to negate the hypertensive effect of norepinephrine. The clinician should be aware of the possibility that tachycardia could be a presenting symptom in pheochromocytoma although the patient is normotensive.

Age Limit and Radiotherapy Option for Sarcomatoid Carcinoma of the Larynx: A Case Report with Literature Review.

Sarcomatoid carcinomas, also known as spindle cell carcinomas (SPCCs), are rare carcinomas, predominantly developing in the lung. They have lots of features of sarcoma in their histological features. The standard laryngeal carcinoma classification is based on tumor size, lymph node affection, and metastasis (TNM), it is the classification scheme of the American Joint Committee on Cancer Staging (AJCC), and it is used in the same way for stage spindle cell carcinoma (SPCC). We present a case report of a young female along with a literature review of sarcomatoid carcinoma of the larynx.